Phosphorus oxychloride → HCID 90041044, compound

HRID 1485880Notes

Reaction equation

HRID 1485880 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]1[C:17](O)=[O:18])=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:20][C:21]1[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[C:22]=1[NH2:23].O=P(Cl)(Cl)Cl>N1C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]1[C:17](=[O:18])[NH:23][C:22]1[C:21]([F:20])=[CH:27][CH:26]=[CH:25][C:24]=1[F:28])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 796472,6-DifluoroanilineHCID 27559672-((tert-butoxy)carbonyl)-2,3-dihydro-1H-isoindole-1-carboxylic acid

Product 1

HCID 90041044HCID 90041044, compoundYield 64.9%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of 2-(tert-butoxycarbonyl)isoindoline-1-carboxylic acid (500 mg, 1.9 mmol, Eq: 1.00) and 2,6-difluoroaniline (294 mg, 2.28 mmol, Eq: 1.2) in pyridine (10 mL) at 0° C. was added POCl3 (437 mg, 266 μL, 2.85 mmol, Eq: 1.5). The reaction was warmed to RT and stirred for 2 h. The mixture was evaporated and water was added and the resulting mixture was extracted with EtOAc. The combined organics were washed with water, brine, dried with MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography to give 1-(2,6-difluoro-phenylcarbamoyl)-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester (462 mg) as a light yellow foam.

Workup

  1. customThe mixture was evaporated
  2. additionwater was added
  3. extractionthe resulting mixture was extracted with EtOAc
  4. washThe combined organics were washed with water, brine
  5. dry with materialdried with MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by flash chromatography

Sources & evidence

ORD record
ord-b7ffcb0902b14ffca12fd325a37c7b08
Source dataset
uspto-grants-2016_08
Patent number
US09422332B2

Reaction notes

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